By Elie Dolgin

ORLANDO, FLORIDA — Basal cell carcinoma is the most common form of skin cancer, but in people with a hereditary predisposition to this disease, lesions crop up so fast that they can hardly keep pace with their doctor’s appointments. “Surgery can become tedious, and often, because of that, people don’t go as often as they should and the [cancerous] areas grow larger,” says Maria Michalowski, a former board member of the Basal Cell Carcinoma Nevus Syndrome (BCCNS) Life Support Network who herself suffers from the disease.

Yet, judging by trial results reported here last month at the annual meeting of the American Association for Cancer Research (AACR), pharmaceutical options on the horizon may preclude the need for regular surgery. In a phase 2 study of 41 people with BCCNS, a team led by Ervin Epstein from the Children’s Hospital Oakland Research Institute in California found that participants taking an experimental Genentech drug called vismodegib developed only four new tumors on average over the course of a year, compared to 24 in subjects on placebo. Plus, subjects taking the drug saw their existing skin lesions shrink dramatically, whereas those on the dummy pill experienced modest growths. “Indeed, there was a tremendous reduction in new lesions,” says Epstein. “The people on the drug had no surgeries. The difference was dramatic.”

Vismodegib, also commonly referred to as GDC-0449, works by inhibiting signaling in the so-called Hedgehog pathway, which regulates cell growth and differentiation. Mutations in this pathway are responsible for some cases of BCCNS as well as a form of brain cancer known as medulloblastoma. And, indeed, vismodegib has also been shown to benefit a young man with the latter disease (N. Engl. J. Med. 361, 1173–1178, 2009).

But even when no such mutations are present, aberrant Hedgehog signaling can still drive solid tumors, for example by supporting the blood vessels that fuel their growth. That’s why Genentech, a San Francisco–based subsidiary of the Swiss pharma giant Roche, is currently testing its drug for nearly 20 other types of cancer.

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Image: USDA Forest Service